N6-(3-iodobenzyl)-9-[β-D-ribofuranosyl]-adenine | 163152-30-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N6-(3-iodobenzyl)-9-[β-D-ribofuranosyl]-adenine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-(3-iodobenzylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(3-iodophenyl)methylamino]purin-9-yl]oxolane-3,4-diol
• CAS: 163152-30-5
• 化学式: C₁₇H₁₈IN₅O₄
• 分子量: 483.266
• InChiKey: TWLWIJNPUVZDOB-LSCFUAHRSA-N

物化性质

• 熔点：
  169-172 °C
• 沸点：
  742.4±70.0 °C(Predicted)
• 密度：
  2.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N6-(3-iodobenzyl)-9-[β-D-ribofuranosyl]-adenine 在 吡啶 、 sodium hydroxide 、 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 5'-deoxy-N⁶-(3-iodobenzyl)-5'-(n-propylthio)adenosine
  参考文献：
  名称：

  N⁶,5‘-Disubstituted Adenosine Derivatives as Partial Agonists for the Human Adenosine A₃ Receptor

  摘要：

  5'-(Alkylthio)-substituted analogues of N-6-benzyl- and N-6-(3-iodobenzyl)adenosine were synthesized in 37-61% overall yields. The affinities of these compounds for the adenosine A(1), A(2A), and A(3) receptors were determined using rat brain cortex, rat brain striata, and stably transfected human A(3) receptors in HEK 293 cells, respectively. The compounds proved to be selective for the adenosine A(3) receptor and displayed affinities in the nanomolar range. Compounds 8, 10, and 11 had the highest affinities for the A(3) receptor with K-i values ranging from 8.8 to 27.7 nM. In the N-6-benzyl series, compound 4 (LUF 5403), with a 5'-methylthio group, maintained a reasonable affinity and had the highest selectivity for the A(3) receptor. Compound 12 (LUF 5411), with an N-6-(3-iodobenzyl) group and a 5'-(n-propylthio) substituent, had the highest A(3) selectivity of all of the compounds and also displayed high affinity for this receptor (K-i = 44.3 nM). The compounds were also evaluated for their ability to stimulate [S-35]GTP gamma[S] binding in cell membranes expressing the human adenosine A(3) receptor. It appeared that the N-6,5'-disubstituted adenosine derivatives behaved as partial agonists. Compounds 2, 4, 8, and 10 had the highest intrinsic activities. Additionally, when tested in a cAMP assay, these compounds also behaved as partial agonists.

  DOI：

  10.1021/jm981090+
• 作为产物：
  描述：

  ((3aR,4R,6R,6aR)-6-(6-(3-iodobenzylamino)-9H-purine-9-yl)2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 在 溶剂黄146 作用下， 反应 12.0h， 以76.95%的产率得到N6-(3-iodobenzyl)-9-[β-D-ribofuranosyl]-adenine
  参考文献：
  名称：

  신규한 아데닌 유도체 및 그 용도

  摘要：

  本发明涉及新的腺嘌呤衍生物及其药理用途，更详细地说，涉及具有化学式1结构式的新的腺嘌呤衍生物或其药学上可接受的盐，以及用于预防或治疗退行性脑疾病的组合物。根据本发明的新腺嘌呤衍生物及其药学上可接受的盐作为腺苷A3受体激动剂，具有抑制炎症细胞（微胶质细胞、巨噬细胞和中性粒细胞等）向疾病部位的迁移和活化作用。此外，根据本发明的腺嘌呤衍生物在脑缺血实验模型中显示出明显抑制和治疗脑损伤的效果，即使在脑缺血后10小时内投药也显示出显著效果，并且已确认可延长脑缺血导致的脑损伤的生存时间，因此可用于治疗和预防包括脑卒中在内的退行性脑疾病，具有实用价值。

  公开号：

  KR20150010195A

文献信息

• A3 adenosine receptor agonists
  申请人：The United States of America as represented by the Department of Health

  公开号：US05773423A1

  公开（公告）日：1998-06-30

  The present invention provides N.sup.6 -benzyladenosine-5'-N-uronamide and related substituted compounds, particularly those containing substituents on the benzyl and/or uronamide groups, and modified xanthine ribosides, as well as pharmaceutical compositions containing such compounds. The present invention also provides a method of selectively activating an A.sub.3 adenosine receptor in a mammal, which method comprises acutely or chronically administering to a mammal in need of selective activation of its A.sub.3 adenosine receptor a therapeutically effective amount of a compound which binds with the A.sub.3 receptor so as to stimulate an A.sub.3 receptor-dependent response.

  本发明提供了N.sup.6-苄基腺苷-5'-N-醛脲和相关的取代化合物，特别是那些在苄基和/或醛脲基团上含有取代基的化合物，以及修饰的黄嘌呤核糖苷，以及含有这些化合物的药物组合物。本发明还提供了一种在哺乳动物中选择性激活A.sub.3腺苷受体的方法，该方法包括向需要选择性激活其A.sub.3腺苷受体的哺乳动物急性或慢性地给予与A.sub.3受体结合的化合物的治疗有效量，以刺激A.sub.3受体依赖的反应。
• 2-Substitution of N6-Benzyladenosine-5'-uronamides Enhances Selectivity for A3 Adenosine Receptors
  作者：Hea O. Kim、Xiao-duo Ji、Suhaib M. Siddiqi、Mark E. Olah、Gary L. Stiles、Kenneth A. Jacobson

  DOI：10.1021/jm00047a018

  日期：1994.10

  Adenosine derivatives bearing an N6-(3-iodobenzyl) group, reported to enhance the affinity of adenosine-5'-uronamide analogues as agonists at A3 adenosine receptors (J. Med. Chem. 1994, 37, 636-646), were synthesized starting from methyl beta-D-ribofuranoside in 10 steps. Binding affinities at A1 and A2a receptors in rat brain membranes and at cloned rat A3 receptors from stably transfected CHO cells

  合成了带有 N6-(3-碘苄基) 基团的腺苷衍生物，据报道可增强腺苷-5'-糖醛酰胺类似物作为 A3 腺苷受体激动剂的亲和力 (J. Med. Chem. 1994, 37, 636-646)从甲基β-D-呋喃核苷开始，分10步。比较了大鼠脑膜中 A1 和 A2a 受体以及来自稳定转染的 CHO 细胞的克隆大鼠 A3 受体的结合亲和力。 N6-(3-碘苄基)腺苷对 A3 受体的选择性是 A1 或 A2a 受体的 2 倍；因此，它是第一个具有任何 A3 选择性的单取代腺苷类似物。探索了 2-取代与 N6-和 5'-位修饰相结合的效果。 2-氯-N6-(3-碘苄基)腺苷的 Ki 值为 1.4 nM，对 A3 受体具有中等选择性。 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide 的 Ki 值为 0.33 nM，对 A3 和 A1 和
• Methanocarba cycloakyl nucleoside analogues
  申请人：——

  公开号：US20030216412A1

  公开（公告）日：2003-11-20

  The present invention provides novel nucleoside and nucleotide derivatives that are useful agonists or antagonists of P1 or P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloakyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A 2B , A 3 , P2Y 2 receptors), cancer (through A 3 , P2 receptors), cardiac arrhythmias (through A 1 receptors), cardiac ischemia (through A 1 , A 3 receptors), epilepsy (through A 1 , P2X receptors), and Huntington's Disease (through A 2A receptors).

  本发明提供了新型的核苷酸和核苷酸衍生物，它们是P1或P2受体的有用的激动剂或拮抗剂。例如，本发明提供了一个式为A-M的化合物，其中A是修饰过的腺嘌呤或尿嘧啶，M是一个约束的环烷基团。腺嘌呤或尿嘧啶与约束的环烷基团相结合。本发明的化合物在治疗或预防各种疾病方面是有用的，包括空气道疾病（通过A2B，A3，P2Y2受体），癌症（通过A3，P2受体），心律失常（通过A1受体），心肌缺血（通过A1，A3受体），癫痫（通过A1，P2X受体）和亨廷顿病（通过A2A受体）。
• Substitution derivatives of n6-benzyladenosine, methods of their preparation, their use for preparation of drugs, cosmetic preparations and growth regulators, pharmaceutical preparations, cosmetic preparations and growth regulators containing these compounds
  申请人：Dolezal Karel

  公开号：US20060166925A1

  公开（公告）日：2006-07-27

  The invention concerns novel substitution derivatives of N 6 -benzyladenosine having anticancer, mitotic, immunosuppressive and antisenescent properties for plant, animal and human cells. This invention also relates to the methods of preparation of these N 6 -benzyladenosine derivatives and their use as drugs, cosmetic preparations and growth regulators comprising these derivatives as active compound and use of these derivatives for preparation of pharmaceutical compositions, in biotechnological processes, in cosmetics and in agriculture.

  本发明涉及 N 6 -苄基腺苷的新型取代衍生物，这些衍生物对植物、动物和人体细胞具有抗癌、有丝分裂、免疫抑制和抗增殖特性。本发明还涉及这些 N 6 -苄基腺苷的制备方法。 6 -苄基腺苷衍生物的制备方法，以及它们作为药物、化妆品制剂和生长调节剂的用途，包括这些衍生物作为活性化合物，以及这些衍生物在制备药物组合物、生物技术过程、化妆品和农业中的用途。
• Preparation, biological activity and endogenous occurrence of N6-benzyladenosines
  作者：Karel Doležal、Igor Popa、Eva Hauserová、Lukáš Spíchal、Kuheli Chakrabarty、Ondřej Novák、Vladimír Kryštof、Jiří Voller、Jan Holub、Miroslav Strnad

  DOI：10.1016/j.bmc.2007.03.038

  日期：2007.6

  Cytokinin activity of forty-eight 6-benzyladenosine derivatives at both the receptor and cellular levels as well as their anticancer properties were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine riboside with corresponding substituted benzylamines and characterized by standard collection of physico-chemical methods. The majority of synthesized derivatives exhibited high activity in all three of the cytokinin bioassays used (tobacco callus, wheat leaf senescence and Amaranthus bioassay). The highest activities were observed in the senescence bioassay. For several of the compounds tested, significant differences in activity were found between the bioassays used, indicating that diverse recognition systems may operate. This suggests that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. In contrast to their high activity in bioassays, the tested compounds were recognized with only very low sensitivity in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The prepared derivatives were also investigated for their antiproliferative properties on cancer and normal cell lines. Several of them showed very strong cytotoxic activity against various cancer cell lines. On the other hand, they were not cytotoxic for normal murine fibroblast (NIH/3T3) cell line. This anticancer activity of cytokinin ribosides may be important, given that several of them occur as endogenous compounds in different organisms. (c) 2007 Elsevier Ltd. All rights reserved.